Endo: Adrenal Pharm

Question 1

For immunosuppression, do you want an agent with glucocorticoid activity, mineralocorticoid activity, or both?

Can you avoid the metabolic effects?

Answer 1

Glucocorticoid activity only

*You can pick an agent with no mineralocorticoid effects, but you can’t pick an agent without metabolic effects

Question 2

Compare the anti-inflammatory activity of prednisone, dexamethasone, and fludrocortisone

Answer 2

• DXM has most anti-inflammatory action
• Fludrocortisone next
• Prednisone has least anti-inflammatory action

Question 3

Compare the mineralocorticoid (aldosterone) activity of prednisone, dexamethasone, and fludrocortisone

Answer 3

• Fludrocortisone has the most aldosterone activity
• Prednisone has some aldosterone activity
• DXM has zero aldosterone activity

Question 4

Which steroid requires activation by the liver?

Answer 4

Prednisone

Question 5

Tx of acute adrenal crisis (3)

Answer 5

• Saline
• IV hydrocortisone if known adrenal problem
• Dexamethasone otherwise
  
  • b/c it won’t interfere with testing

Question 6

Tx of Addison’s disease (4)

Answer 6

• Oral hydrocortisone, DXM, or prednisone
  
  • Add fludrocortisone if pt needs more aldosterone effects (hypotensive)
• Add DHEA in women
• Increase dose during illness

Question 7

Name 3 drug classes that can be used to treat Cushing’s syndrome

Answer 7

• Cortisol synthesis inhibitors: Ketoconazole, metyrapone, etomidate
• Cortisol receptor blocker: Mifepristone
• Somatostatin Analog: Pasireotide (inhibit ACTH release)

Question 8

Ketoconazole: mechanism and ADR (3)

Answer 8

• Ketoconazole is a C17-20 desmolase inhibitor (inhibits cortisol synthesis)
• ADR: GI upset, gynecomastia/impotence, hepatotoxic
  
  • Testosterone synthesis may be inhibited too

Question 9

Metyrapone: mechanism and ADR (3)

Answer 9

• Inhibits 11beta hydroxylase, decreasing cortisol synthesis
• ADR: Hirsutism, Na retention, hypertension
  
  • Can increase androgen and aldosterone-like-peptide synthesis

Question 10

Name one drug in the tx of hypercortisolemia that inhibits CYP450

Answer 10

Ketoconazole

Question 11

Describe one adverse effect of long-term glucocorticoid therapy

Answer 11

• Pharamacologic doses of glucocorticoids suppresses the HPA axis
• Lack of ACTH causes adrenal atrophy
• When exogenous steroid is removed, it takes a long time before adrenal wakes up again

Question 12

Name 3 signs of aldosterone excess

Answer 12

Hypertension (excess Na retention)

Hypokalemia

Metabolic alkalosis

Question 13

What steroid has the most anti-inflammatory and least aldosterone properties?

Answer 13

Dexamethasone

Question 14

Name 3 signs of adrenal crisis

Answer 14

Hyponatremia

Hyperkalemia

Decreased volume status

Question 15

Mifepristone MOA

Answer 15

Blocks cortisol receptor

Question 16

Compare the MOA of two different classes of anti-aldosterone drugs

What effect do these drugs have on K?

Answer 16

• Amiloride, triamterene: inhibit ENa channel
• Spironolactone, eplerenone: inhibit aldosterone receptor

These drugs all raise plasma potassium (useful b/c hyperaldosteronism pts have hypokalemia)

Question 17

What medication is used to manage the hypertension associated with hyperaldosteronism?

Answer 17

Calcium channel blockers (-dipines)

Question 18

Describe the pharmacologic treatment prior to surgical removal of a pheochromocytoma (3)

Answer 18

1. Phenoxybenzamine (irreversible, non-selective) or doxazosin (alpha1 only)
2. AFTER, metoprolol or labetalol
3. Give Nicardipine if blood pressure still too high

Question 19

What drug can be used for non-surgical tx of pheochromocytoma?

MOA?

Answer 19

Metyrosine, which inhibits catecholamine synthesis by inhibiting tyrosine hydroxylase